Alkaloids

Anthranilic acid is found to be a key intermediate in the biosynthesis of L-tryptophan. Therefore, it has been established that this biotransformation issolely responsible to the elaboration of the indole alkaloids.

Alkaloids derived from anthranilic acid

Alkaloids derived from anthranilic acid

A number of these alkaloids, mostly found in the Rutaceae and the citrusfamily.

The alkaloids derived from anthranilic acid may be classified into threemajor categories, namely:

1. Quinazoline alkaloids2. Quinoline alkaloids3. Acridine alkaloids

Other alkaloids Pyrroloquinazolines Quinazolinocarbolines Furanoquinolines Acridone alkaloids Anthranilic acid proto-

alkaloids (e.g. damascenin)

O

OH

NH2 NH

O

NH2

OH

N

N

N N

anthranilic acid L-tryptophan

quinazoline quinoline acridine

Quinazoline alkaloids

The antibacterial activity of different parts of Peganum harmala, including seed, root,flower, leaf and stem has been investigated and compared. Among the evaluated differentparts of P. harmala, the seed and root extracts showed the best antibacterial activityagainst Gram positive bacterial species, including Bacillus anthracis, Bacillus cereus,Bacillus pumilus, Staphylococcus aureus, Staphylococcus epidermidis, Listeriamonocytogenes and Streptococcus pyogenes and Gram negative bacterial species,including Pseudomonas aeruginosa, Brucella melitensis, Proteus mirabilis, Salmonellatyphi, Escherichia coli and Klebsiella pneumonia (Darabpour et al., 2011.)

Other alkaloids derived from anthranilic acid

Vasicine

It is mostly used as an expectorant and bronchodilator.Vasicine also shows abortifacient action which is due to the release ofprostaglandins.

Other alkaloids derived from anthranilic acid

How does rutaecarpine? - Selective COX2 inhibitor.

Quinoline alkaloids

In general, the alkaloids containingessentially the ‘quinoline’ nucleusinclude a series of alkaloids obtainedexclusively from the Cinchona bark,the major members of this particulargroup are, namely: quinine, quinidine,cinchonine and cinchonidine.Uses

1. It is used as a flavour in carbonatedbeverages.2. It is widely used as an antimalarialagent in tropical countries.3. It is employed as a skeletal musclerelaxant.

Acridine alkaloids

Uses1. In Chinese medicine rue is considered as an emmenagogue, intestinalantispasmodic, sedative, uterine stimulant, vermifuge, rheumatism, cold and fever.2. In Poland, it is used as an aphrodisiac and choleretic.3. The herb is used medicinally as a bitters, an aromatic stimulant, ecbolic and insuppression of the menses.

Other alkaloids derived from anthranilic acid

In Ruta graveolens L.: Rutacridone epoxide wasfound to be a direct acting mutagen in Salmonellatyphimurium strains (TA98, TA100 and TA1538).Evidence is presented that rutacridone ismetabolized by rat liver enzymes to thecorresponding epoxide as the ultimate mutagen.

Other alkaloids derived from anthranilic acid

protoalkaloid

Active substances of Nigella sativa are anthranilic derivatives damascenin,metildamascenin, nigellin, damascinin, fatty oils, low saponin.

Application: in case of gastro-enteritis, carminativum, diureticum, galactogogum.

Pepper-like spice.Homeopathy

Plants with anthranilic acid derived alkaloids

Peganum harmala, Zygophyllaceae, drugs are the flower and fruit

Skimmia japonica, Rutaceae, drug is the fruit

Ptelea trifoliata, wafer ash, Rutaceae, branch with fruit

Nigella damascena, Ranunculaceae, drug is the flower

Peganum harmalaZygophyllaceae

Peganum harmala is of Asian Origin,commonly called e.g. esfand, wild rue,Syrian rue.

The plant has remained a popular toolin both folk medicine and spiritualpractices for so long that somehistorians believe the plant may be theancient „soma" - a Vedic ritual drink -a medicinal aid that is mentioned in avariety of ancient Indo Iranian texts.

It is a perennial plant which can grow to about 0.8 m tall, but normally it is about0.3 m tall. The roots of the plant can reach a depth of up to 6.1 m, if the soil whereit is growing is very dry. It blossoms between June and August in the NorthenHemisphere. The flowers are white and are about 2.5–3.8 cm in diameter. Theround seed capsules measure about 1–1.5 cm in diameter, have three chambersand carry more than 50 seeds.It has spread invasively to America. "

Peganum harmalafruit

Peganum harmala branch with fruit have been used to treatpain and to treat skin inflammations, including skin andother cancers.Peganum harmala has been used as an emmenagogue andabortifacient agent. The "root is applied to kill lice” inhibitthe reproduction of the Tribolium castaneum beetle.

It is also used as an anthelmintic. In large quantities, it canreduce spermatogenesis and male fertility in rats.

Some alkaloids of harmal seeds are monoamine oxidase Ainhibitors, e.g. harmaline.

Tribolium castaneum

For sale at a market inKazakhstan

It is the "Turkey red„ - from the seeds is often used in western Asia to dye carpets andwool.The stems, roots and seeds can be used to make inks, stains and tattoos.

luminescence

Pyrroloquinazoline alkaloids

Vasicine (peganine!)

It also shows oxytocic properties very similar to those exhibited by oxytocin and methylergometrine.Vasicine also shows abortifacient action which is due to the release of prostaglandins.

VasicinoneIt is used mainly as an expectorant which action is solely due to stimulation of the bronchialglands.

Skimmia japonicaRutaceae

Skimmia japonica, the Japanese skimmia, is a species of flowering plant in the familyRutaceae, native to Japan, China and south east Asia.Growing to 6 m tall and wide, it is a rounded evergreen shrub with glossy, leatheryleaves widely cultivated as an ornamental plant in gardens and parks.Its fragrant flowers can be cream-yellow to white, followed on female plants by smallround, red fruits.Its characteristic alkaloids are skimmianine and dictamnine furanoquinolines.

Some furoquinoline alkaloids have beenfound to have in vivo pharmacologicalproperties such as antimicrobial, antiviral,mutagenic and cytotoxic activities.

Dictamnine has the property of causingsmooth muscle contraction.Skimmianine shows acetylcholinesteraseinhibition.

Ptelea trifoliata (branch with fruit), the common hoptree,native to North and Central America (Mississippi RiverValley). It is a deciduous shrub or tree, growing to 6-8 m tallby 4 m wide.

The plant has thick fleshy roots, flourishes in rich, rathermoist soil. Its juices are acrid and bitter and the bark possessestonic properties.

Ptelea trifoliataRutaceae

Important alkaloids from Ptelea trifoliata

Nigella damascenaRanunculaceae

flower

Nigella damascena is an annual garden floweringplant, belonging to the buttercup familyRanunculaceae.Nigella damascena is an easily grown plant andwidely cultivated throughout the temperateworld, and numerous cultivars have beendeveloped for garden use.

It is native to southern Europe, north Africa andsouthwest Asia, where it is found on neglected,damp patches of land.

It grows to 20–50 cm tall, with pinnately divided,thread-like, alternate leaves.

The flowers, blooming in early summer, are mostcommonly different shades of blue, but can bewhite, pink, or pale purple, with 5 to 25 sepals.

The fruit is a large and inflated capsule, growingfrom a compound ovary, and is composed ofseveral united follicles, each containing numerousseeds.

Its characteristic alkaloid isdamascenin - as a panaceae.

The amino acid L-histidine containing the heterocyclic imidazole ring, isconsidered to be the right precursor of alkaloids that essentially comprise ofthis ring-system.

Alkaloids derived from histidine

Pilocarpus jaborandiRutaceae

Pilocarpus species, belonging to family Rutaceae, found to contain a lot of alkaloidswith an imidazole ring, namely: pilocarpine, isopilocarpine, and pilosene.

Alkaloids are located mostly in the upper epidermal part of the leaves.

It has been observed that the alkaloids in these species invariably reside in the leaves.Pilocarpine constitutes 0.5-1.0% of the dried leaf material.Isopilocarpine appears to vary significantly within a range from 5 to 7.5% of the totalalkaloids.

When photophobia from a dilated pupil is a problem,topical dilute pilocarpine (0.1%) may be helpful.

In glaucoma therapy pilocarpine can be used.

Glaucoma is the condition in which pressure builds up inside the eye. It often affectsonly one eye. Warning signs are blurred vision or haloes around lights, particularly atnight. Untreated condition may cause blindness.

Together with pilocarpine treatment, the drug acetazolamide may be used to reduce theformation of aqueous humour, the fluid inside the eye, reduce the intra-ocular pressurein glaucoma patients.Pilocarpine possesses miotic and diaphoretic actions.Pilocarpine nitrate is used extensively as an ophthalmic drug having cholinergic action.

glaucoma Therapy with pilocarpine

Terpene derived pseudoalkaloids

Compounds not derived from amino acids, the aminoacid’s N-atom is a new part of a heterocycle.

The species are taxonomically diverse and differ from eachother considerably.

Pseudoalkaloids

diterpene alkaloids: Aconitum species

Taxus species

steroid alkaloids : Solanum species

Veratrum species

Sabadille species

C-nor-D-homosteroid-alkaloids:

Biosynthesis of terpenoids

Aconitum napellus L.RanunculaceaeAconiti tubermonkshood

The Aconitum napellus is native perennial plant inSouthern Europe and Asia's high mountains. It isgrown in the US and Canada as an ornamentalplant.

The plant is 0.5-1.5 m high. Its dark green leavesare digitate. Its flowers are blue raceme. Theplant has two tubers. The drug is the tuber, whichis dark brown across the top and along the lengthis wrinkles.

subalpine flower

Content0.2-3% diterpenoid alkaloids

the principal alkaloid: aconitine (diester)

hypaconitine

mezaconite

neopelline

napelline

neoline

sembusin A

phenylalanine alkaloid magnoflorine

inosite, sugars, resin, plant acids.Product

Aconiti tuber

Lethal dose of aconitine inmice: LD50: 0.12 mg/kg

In adults 1-2 g bulb causesfatal poisoning.

Therapeutic uses: in chronic arthritis

in intercostal and trigeminal neuralgia

Poisoning

The aconitine is very strong poison. Lethal dose is 1.5-1.6 mg in humans. The drugitself is not being used because of the risk of poisoning.

Smaller doses of aconitine cause bradycardia, hypotension, respiratory paralysis,later cardiac arrest.

Aconite has long been used in traditional Chinese medicine and Ayurveda (Hindutraditional medicine). Aconite was also described in Greek and Roman medicine byTheophrastus, Dioscorides.

Aconiti tuber

Nowadays the Chinese and Ayurvedicmedicine like to use the aconite preparations,which can be toxic.

Some honeys contain pollen-aconiti andaconitine can be detected.

Symptoms:Toxic effect occurs during 10-20 minutes.

Burning feeling in the mouth, tingling in the limb fingers, which spreads to theentire body. Insensitivity occurs againts pain. Body temperature diminishes andshivering occurs.

Nausea, vomiting, diarrhea, and high urination frequency are characteristic.Tachycardia arrhythmia, impaired vision will be. After six hours cardiac andrespiratory arrest can be observed.

Treatment of poisoning is mainly supportive. All patients require close monitoringof blood pressure and cardiac rhyrthm. Gastrointestinal decontamination withactivated charcoal can be used if given within one hour of ingestion.

Taxus baccata L.Taxaceae

Taxi bracteae folium

Evergreen dioecious, stronglybranched tree.

The tree is spread in Western Europe’s parks,gardens.approx. 15 m tall coniferous trees.pine-neddle: 2 mm wide, 35 mm longcolor: shiny, dark greenflip side: light green, matt (stomata)seeds: dark brown, juicy, sweet taste and slimythe seeds are surrounded with scarlet aril

Taxus baccata L.(Taxaceae)

"Tree of Death"

Taxus baccata is a conifer native to western, central and southern Europe, northwestAfrica, northern Iran and southwest Asia.

It is the tree originally known as yew.

All parts of a yew plant are toxic to humans with the exception of the yew red arillus.Taxanes are widely used as chemotherapy agents.Taxol and semisynthetic Taxotere have anticancerous properties:

1. kill the cancerous cells2. inhibit the cell proliferation

Toxic molecules can be found in the seeds and leaves.

molecules of the yew:Diterpenes (= ester alkaloids) with N atom:

taxin A, taxin B, taxol A, taxol Bbiflavonoids:

sciadopitizin, ginkgetin, sekojaflavonother phenols:

catechin, betuloside, taxikatinsterane-type compounds:

ecdysteronCyanogen glycosides(Polysaccharides, lipids, sterols)

Taxus baccata L.(Taxaceae)

yew

Products and applyingTaxus baccata L.

(Taxaceae)

50-100 g pine-neddle arelethal dose for an adult.

Taxanes accelerate the assembly ofmicrotubules from tubulin dimers.These are microtubule stabilizers. The fixedstructure does not allow dynamicmicrotubule remodeling required for theproliferation process.

Antihistamine pretreatment and steroidtherapy are necessary before taxanetreatment in ovarian carcinoma!

Taxotere (docetaxel) is applied in mammacarcinoma.Taxotere is prepared from the baccatin III(by semi-synthetic mode)

Intermediate filaments are responsiblefor the three-dimensional structure.

In addition, they are also involved in theformation of junction.

• Cytoskeleton is involved in many cellsignalling pathways,

• in the uptake of extracellular material(endocytosis),

• segregates chromosomes during cellulardivision,

• is involved in cytokinesis (the division ofa mother cell into two daughter cells),

• provides a scaffold to organize thecontents of the cell in space and forintracellular transport (for example, themovement of vesicles and organelleswithin the cell);

• and can be a template for theconstruction of a cell wall.

Symptoms of poisoning of Taxus-toxine:

Taxus baccata L.(Taxaceae)

Seeds of Taxus baccata

The drug is used in folk medicine as:anthelminticexpectoration,epilepsy,againts menstruation painagainst diphtheria,tonsillitis,wound healing (externally)

India is used as a control of fertility.Direct use is dangerous!The LD50 of taxine B 4.5 mg/kg iv. in rats.

Activated charcoal may be detoxified successfully several hours after the poisoning!

The Taxaceae extracts stimulate the smooth muscle and striated muscle.Its effect causes paralysis of cadiac muscle.The compound irritates the respiratory center, and late paralyzes.The compounds are strongly irritate the gastro-intestinal mucosa, kidney and uterus.The cause of death is cardio-respiratory arrest.The pupils dilate during the poisoning.

The semi-synthetic product derived fromTaxus baccata (yew) is docetaxel.Both products build up from taxane ring(6-8-6) and phenylisoserine.

pharmaceutical formsTaxus brevifoliais Pacific evergreen. Thetaxol is isolated from thebark.Taxol is poorly absorbedparenterally, causesallergenic or other seriousside effects.Paclitaxel is a semi-synthetic product of taxol

Side effects:

- hypersensitivity reactions in 20%of patients- dyspnoe, hypertension, chest pain,fatigue, muscle pain- This should be treatedimmediately (dexamethasone inadvance, and then histamine H2antagonist).- peripheral neuropathy, alopecia,nausea

Sterane skeleton

(cyclopentane perhydro phenanthrene)

pseudoalkaloids

Steroid alkaloids

Steroid alkaloids

Steroid alkaloids have a fairly complex nitrogen containing nucleus.

Two important classes of steroid alkaloids arethe Solanum type - one example is solanidine.

Veratrum type - there are more than 50 Veratrum alkaloids, examplesare veratramine, jervine

This steroid alkaloid is the nucleus (i.e. aglycone) for two importantglycoalkaloids, solanine and chaconine, found in potatoes.

Other plants in the Solanum family including various nightshades,Jerusalem cherries, and tomatoes also contain solanum-type glycoalkaloids.

Glycoalkaloids are glycosides of alkaloids.

Where poisons are found?

Production of solanum-type glycoalkaloids is favored by the sameconditions that promote the development of chlorphyll. Therefore,the concentration of these glycoalkaloids is highest in potato sproutsand green potato skins, and tomato vines and green tomatoes.

Care should be taken to prevent the exposure of potatoes to sunlight.

These alkaloids are not destroyed by cooking or drying at hightemperatures.

Solanum-type alkaloids are foundin plants in the form of glycosidesof alkaloids.

Solanine and chaconine causepoisoning in potatoes.

They have the same aglycone,solanidine, but the structure oftheir carbohydrate sidechains isdifferent.

Tomatine is a glycoalkaloid foundin tomatoes. Its aglycone istomatidine.

Solanum dulcamara L.Solanaceae

Woody Nightshadevery common species

Solanum dulcamara, also known as bittersweet or climbingnightshade, is a species of vine in the potato genus Solanum,family Solanaceae.It is native to Europe and Asia, and widely naturalised,including North America, where it is an invasive problemweed.

Bittersweet is a semi-woody herbaceous perennial vine, which scrambles over otherplants, capable of reaching a height of 4 m where suitable support is available, but moreoften 1–2 m high.

The flowers have prominent tube-like stamens, five purple petals with a yellow mark atthe base. Small red berries are gathered in bunches.The leaves are 4–12 cm long, roughly arrowhead-shaped, and often lobed at the base.The herbaceous plant has dimorphic leaves.They are entire or trilobate depending on their position on the stem.

The fruit is an ovoid red berry about 1 cm long, soft andjuicy, with the aspect and odor of a tiny tomato, and ediblefor some birds, which disperse the seeds widely.

The berry is poisonous to humans and livestock, and theberry's attractive and familiar look make it dangerous forchildren.

Biological activity

The stems are used external as supportive therapy in chronic eczema.

The alkaloids, solanine (from unripe fruits), solasodine (from flowers) and beta-solamarine (from roots) inhibited the growth of bacteria eg. E. coli and S. aureus.

Solanine and solasodine show antidermatophytic activity against Chrysosporium,Trichophyton, thus it may cure ringworm.

Content:steroid-glykoalkaloidssteroid saponins by their aglycons:

tomatidenol, soladulcidine, solasodinsaponins

Solanum dulcamara L.Solanaceaenightshade

Medical application: rheumatism, arthritis, cervical lymphnode swelling, skin diseases, eczema, psoriasis, herpesDose:1g single dose - daily dose is 1-3 g (infusion)

The molecules have characteristic properties of steroid saponins.

Tomatidenol is anti-carcinoid type molecule.

Components of glycosides are 1 mol D-glucose and 2 mol L-ramnose in solamargin

1 mol D-glucose, 1 mol D-galactose and 1 mol L-ramnose in solasonin

Solanum dulcamara is industrial raw material for the production of steroidhormones, anti-inflammatory drugs. (e.g. pregnadienolone acetate)

Solanum dulcamara L.Solanaceaenightshade

Industrial sprout has glycoalkaloid. Content varies between 0.7 to 2.2%.

Solanum laciniatumSolanaceae

Solanum laciniatum produces two types of foliage: large lance-shaped orirregularly lobed juvenile leaves 300 mm long by 250 mm wide and smallergenerally entire lance-shaped adult leaves 150 mm long by about 30-50 mm wide.

Both types of leaf are a rich dark green on the upper surface, and a lighter greenunderneath, with conspicuous veins.

They are held on dark green succulent stems, which turn black, then a rough light-brown, with age.

Solanum laciniatum occurs in temperateregions of New South Wales, theAustralian Capital Territory, Victoria,South Australia, Tasmania, NewZealand and associated islands on arange of soil types.

It forms a large shrub 4 m high by 5 mwide.

Schoenocaulon officinale Schlecht.Liliaceae

Sabadillae semen

Schoenocaulon is a North American genus ofperennial herbaceous flowering plants,ranging from the southern United States toPeru. It is also cultivated.

Merck (1891) isolated two new alkaloids from cevadilla,which he names sabadine and sabadinine respectively.

Schoenocaulon officinale have narrowfibrous foliage and simple raceme.Drug is the wide core with 5-8 mmlong and 1-2 mm size.Odorless bitter, pungent.The endosperm can be found in oil-richseed, which comprises 1-5% of thealkaloids.

sabadine

Schoenocaulon officinale Schlecht.Liliaceae

Sabadille semen

Content: 1-5% alkaloids (cevane type)dominant alkalods are cevadin, veratridin

others: sabadillinsabadinsabadininveratrum- with tiglin-, kelidon-acids

9-17% fatty oilfitosterineresin, wax

Effect: antihypertensiveabnoral heart rhythm balancing effect

Application:neuralgia,against parasitesallergyVeratridine is an insecticide.

Medicinal action and uses:

Sabadilla, or cevadilla is an acrid, drastic emeto-cathartic, in overdoses capableof producing fatal results.

Cevine was found to be less poisonous than cevadine, though producing similarsymptoms.

The powdered seeds have been used as a vermifuge, and to destroy vermin inthe hair, being the principal ingredient of the pulvis capucinorum used inEurope.

Cevadilla was formerly used internally as an anthelmintic, and in rheumaticand neuralgic affections.

The highly poisonous veratria, which is derived from it, has been given inminute doses internally in acute rheumatism and gout, and in someinflammatory diseases, but it must be used with caution.

Veratrum album L.Liliaceae

Veratri rhizomaWhite Hellebore

Plant causes mucous membrane irritation.

Veratrum lives in peaty andboggy areas of Europe and Asia.

The plant is a perennial herb with a stoutvertical rhisome covered with remnants of old leafsheaths. The stout, simple stems are 50 to 175 cm tall.

Resveratrol has been isolated from the plant.

The root is very poisonous, with a paralyzing effect onthe nervous system.

Drugs: rhizomes and roots

monocot root

Veratrum album L.Liliaceae

Veratri rhizoma

Large numbers of roots grow at the bottom of therhizomes; tufts and stout, 3-4 mm thick, and thecolor is bright yellow.

Ca-oxalate rafids in the rhizomes of the drug can beeasily recognizable by microscopic examination.

Veratri rhizoma

Content:1,5-1,6 % alkaloidsester and non ester alkaloids(glycoalkaloids)fatty oilsresinacetic-, butyric-, angelic-,tiglic- acids

The structure of rubijervin and jervin is cyclopentano-perhydro-phenanthrene.

Veratri rhizoma

Physiological effect:

- antihypertensive (alkaminesters)- protoveratrine A and B are used in cases of acute hypertension- alkamine glycosides are less effective- A and B are effective in protoverin

The drug is used mainly in veterinary medicine:- stomachicum in ruminants - emetic in pigs

Alkaloids derived from purine

Coffeae semen RubiaceaeColae semen SterculiaceaeCocoa semen SterculiaceaeTheae folium CamelliaceaeMate folium AguifoliaceaePaullinia sorbilis Sapindaceae

Drugs with alkaloids derived from purine

They bioactive xanthine type alkaloids have marked physiological effects.

What is caffeine?

Caffeine is a drug that is naturally produced in the leaves and seeds of manyplants.

Caffeine is a xanthine alkaloid, found in the bean of coffee plant, the leaves oftea bush and in Cola spp. as well as Mate leaves.

It's also produced artificially and added to certain foods.

Purine is a heterocyclic, aromatic, organic compound, consisting of a pyrimidine ringfused to an imidazole ring.

In its natural form, caffeine tastes verybitter, therefore it induces bilesecretion.

Caffeine is not stored in the body, andits effects for up to 6 hours.

Caffeine is defined as a drug because itstimulates the central nervous system,causing increased alertness.

Caffeine gives most people atemporary energy boost and elevatesmood.

Caffeine is in tea, coffee, chocolate,many soft drinks, and pain relieversand other over-the-countermedications.

Biological effects of caffeine

Caffeine may also cause the body to lose calcium, and that can lead to bone loss overtime. Drinking caffeine - containing soft drinks and coffee instead of milk can havean even greater impact on bone density and the risk of developing osteoporosis.

Caffeine can aggravate certain heart problems.It may also interact with some medications or supplements.In stress or anxious, caffeine can make these feelings worse.

Methylated xanthines (methylxanthines),which include e.g. caffeine, theobromine,and theophylline, affect not only theairways but stimulate heart rate, force ofcontraction, cardiac arrhythmias at highconcentrations.

In high doses they can lead to convulsionsthat are resistant to anticonvulsants.Methylxanthines induce acid and pepsinsecretions in the gastrointestinal tract.

Methylxanthines are metabolized bycytochrome P450 in the liver.

Chemopreventive properties of caffeine in hairless mice after oral or topicaladministration: reduced multiplicity, incidence and volume of tumor,elimination of mutant p53 gene, selected apoptosis of tumor cells.

Tumor suppressor p53

Relationship between caffeine consumption and nonmelanoma skin cancer:

prevalence 9.1% in coffee drinkers vs. 10.2% in non-drinkers.

Demographic and lifestyle variables that affect NMSC.Women’s HealthInitiative StudyGroup (1998)

Moderation is the key!

Caffeine is usually thought to be safe inmoderate amounts. Experts consider 200-300 mg of caffeine a day to be a moderateamount for adults.

Consuming as little as 100 mg of caffeine aday can lead a person to become"dependent" on caffeine.

This means that someone may developwithdrawal symptoms (like tiredness,irritability, and headaches) if he or shequits caffeine suddenly.

Flowering branches of Coffea arabica

Coffea is a genus is a member of the Rubiaceae family.

They are shrubs or small trees native to tropical and southern Africa andtropical Asia.

Coffee is one of the world's mostvaluable and widely tradedcommodity crops and is an importantexport product of several countries.

Coffee is a brewed beverage preparedfrom the roasted seeds of severalspecies of an evergreen shrub of thegenus Coffea.

Coffea have xanthine derivated mayor and minor components

Coffea arabicaRubiaceae

The tree of Coffea arabica will grow fruits after three to fiveyears, and will produce for about 50 to 60 years (although upto 100 years is possible).

The white flowers are highly scented.The fruit takes about 9 months to ripen.

The trees produce red or purple fruits called "cherries„.

The cherries contain two seeds, the so-called "coffee beans",which — despite their name — are not true beans.

In about 5-10% of any crop of coffee cherries, only a singlebean, rather than the usual two, is found.This is called a peaberry, which is smaller and rounder thana normal coffee bean.

It is often removed from the yield and either sold separately(as in New Guinea peaberry), or discarded.

Map showing areas of coffee cultivation

In 2011 Brasil was the world leader in production ofgreen coffee, followed by Vietnam, Indonesia andColombia. Arabica coffee seeds are cultivated in LatinAmerica, easten Africa, Arabia or Asia.

Robusta coffee seeds are grown in western and centralAfrica, throughout southeast Asia and to some extent inBrazil.

Seeds from different countries or regions can usually bedistinguished by differences in flavor, aroma, body andacidity (bitter).

Coffea arabicaRubiaceae

Robusta coffee seeds

Landscape of coffea plantation in Brasil

Plum-shaped fruit is drupe.A crop is two pieces. approx. 2 cm corebeing.The drug is the endosperm.

Structure of coffee berry and beans:1: Center cut.2: Bean (endosperm).3: Silver skin(testa, epidermis).4: Parchment coat(hull, endocarp).5: Pectin layer.6: Pulp (mesocarp).7: Outer skin (percarp, exocarp).

Eaten after roasting. During roasting the coffee to swell, turnbrown, caramelizes the sugars, the flavor (coffee, oil / kaffeol)develop.

After roasting the caffee seeds

alpha furfuryl mercaptan

Evergreen shrub of the genus coffea

Coffee cultivation first took place in southern Arabia.An important export commodity, coffee is the top agricultural export more

than twelve countries.

When grown in the tropics, coffee is a vigorous bush or small tree that usuallygrows to a height of 3–3.5 m. Most commonly cultivated coffee species grow bestat high elevations, but are nevertheless intolerant of freezing temperatures.

Camellia sinensis L.

CamelliaceaeTheae folium

Camellia sinensis is the species of plant whoseleaves and leaf buds are used to produce thepopular beverage tea.

White tea, yellow tea, green tea, oolong andblack tea are all harvested from this species, butare processed differently to attain different levelsof oxidation.

There are two major varieties used for tea, Chinesetea, Camellia sinensis var. sinensis, and Assam tea,Camellia sinensis var. assamica.

var. sinensis has lance shaped, 8-10 cm longleaves.var. assamica has larger longitudinal, pointingleaves.

Leaves are lance or elliptical shaped coriaceousand naked, with neat serrated edges, the main ribprotrudes to the lower surface.

When quite young the leaves may be more or lesshairly.

The drug has a characteristic odour, it has anastringent bitter taste.

Camellia sinensis L. CamelliaceaeTheae folium

var. assamica

var. sinensis

Camellia sinensis is mainly cultivated intropical and subtropical climates, inareas with at least 127 cm of rainfall ayear.

Many high quality teas are grown athigh elevations, up to 1500 meters, asthe plants grow more slowly andacquire more flavour.

Theae folium

green tea

dryingheated in iron pansmachines roll

The green tea is official in pharmacopoeia in several Europen countries.

black teagentle heating and dryingfermentedmachines roll

During fermentation several new moleculesare formed, e.g. tea flavins from catechines,seven membered ring is appeared, and B-ring is formed.

Flavour formation can be formed.One cap of tea has 20-30 mg coffeine.

Contains:coffeine (2.5-3.5%)theobromine (0.1-0.2%)teophylline (0.02-0.04%)

Coffeine can be found with tannin.

Other components:kempferol-, quercetin-, miricetin-glycosides, gallic acids, p-cumaric acids, coffeicacid, klorogenic acids, theogallin, p-coumaroyl chinese acid, chinese acid, 0,5-1%volatile oil, triterpene-saponins, carotenoids, lutein, violaxantin, neoxantin,amino acid derivatives, eg. teanin

green tea:flavanols (catechins), flavon glycosides, little hydrolyzed tannins, saponins, metalelements (Al-fluoride)

black tea:tannin like materials, oxidation derivates of flavanols, tea-flavins, little flavonglycosides, metal elements (Al-fluoride)

Wessner et al. 2004.

Camellia sinensis L.

CamelliaceaeTheae folium

Mate also known as yerba mate etc. is atraditional South American caffeine-richinfused drink, particularly in Argentina,where it is defined by law as the "nationalinfusion”

Uruguay, Paraguay and the southern statesof Brazil and to a lesser degree in south ofChile, the Bolivian Chaco, Syria andLebanon.

It is prepared from steeping dried leaves ofyerba mate, known in Portuguese as erva-mate) in hot water.

Serrated leaves

Ilex paraguariensis St. HilaireAquifoliaceaeMate folium

Yerba mate, begins as a shrub and then matures to atree and can grow up to 15 metres (49 ft) tall.

The leaves are evergreen, 7–11 cm long and 3–5.5 cmwide, with a serrated margin. The leaves are oftencalled yerba (Spanish) or erva (Portuguese), both ofwhich mean "herb". They contain mateine andrelated compounds and are harvested commercially.

The flowers are small, greenish-white, with fourpetals. The fruit is a red drupe 4–6 mm in diameter.

Mate contain

•xanthine alkaloids, 1-2 % caffeine, 0.45-0.9%

•theobromine, 0.05% theophylline, tannin-likesubstances 4-16%

•caffeic and chlorogenic acids,

•the amines choline and trigonelline,

•amino acids,

•the flavonoids kempferol, quecertin and rutin,ursolic acid,

•vitamin B2, B6, C, niacin and pantothenic acid,and volatile oil.

Ilex paraguariensis St. HilaireAquifoliaceaeMate folium

Yerba mate also contains elements such as potassium, magnesium and manganese.

Plantation in Misiones, Argentina

Hot tea consumption is associated with oralcancer esophagus cancer, cancer of the larynxand squamous cell of the head and neck.

Studies show a correlation betweentemperature and likelihood of cancer, makingit unclear how much a role mate itself plays asa carcinogen.

A study by the International Agency forResearch on Cancer showed a limitedcorrelation between oral cancer and thedrinking of large quantities of "hot mate"

Smaller quantities (less than 1 liter daily) werefound to increase risk only slightly, thoughalcohol and tobacco consumption had asynergistic effect on increasing oral, throat,and esophageal cancer.

Problem with hot mate

The edible properties of Theobroma cacao werediscovered over 2000 years ago by the local people ofCentral America living deep in the tropical rainforests.

The scientific name Theobroma cacao was given to thespecies by the Swedish botanist Carl Linnaeus in 1753,when he published it in his famous book SpeciesPlantarum.

Theobroma means "food of the Gods" in Latin, andcacao is derived from the Nahuatl (Aztec language)word xocolatl, from xococ (bitter) and atl (water).

In the year 2008-2009 the world cocoa production was3,515,000 tonnes.

Theobroma cacao L.SterculiaceaeCacao semen

Theobroma cacao L.SterculiaceaeCacao semen

Theobroma cacao, cocoa tree, is a small(4–8 m tall) evergreen tree in thefamily Sterculiaceae native to the deeptropical regions of Central and SouthAmerica.

Leaves are alternate, entire, unlobed, 10–40 cm long and 5–20 cmbroad.The flowers are produced in clusters directly on the trunk and olderbranches; this is known as cauliflory. The flowers are small, 1–2 cm indiameter, with pink calyx.Cacao flowers are pollinated by tiny flies.

crop

The fruit called a cacao pod, is ovoid, 15–30 cm long and 8–10 cm wide, ripeningyellow to orange, and weighs about 500 g when ripe.The pod contains 20 to 60 seeds, usually called "beans", embedded in a whitepulp.The seeds are the main ingredient of chocolate, while the pulp is used in somecountries to prepare a refreshing juice.

Each seed contains a significant amount of fat (40–50%) as cocoa butter. Theirmost noted active constituent is theobromine.

Cacao semen

Its seeds are used to make cocoa powder and chocolate.

Cacao semen

Content:1-3% theobromine0.05-0.35% coffeine45-53% fatty oil4-8% tannins8% starch2.5 % sugarvolatile oil (linalool)amyl acetate, amyl butirate,esters, acids

The seed coat is thin, fragile.The embryo violet-brown color.The embryo with two large cotyledonsfolded, it forms the drug.

Toasted cacao beans produced at the hacienda.

There is no chocolate flavour in cocoa beanswithout fermentation.

When the seeds are dried and fermented inthe sun they are brownish red, and known ascocoa beans.

Chocolate is considered a delicacy for humans, but cocoa solids contain thealkaloid theobromine, which is toxic to pets such as cats and dogs.Excessive amounts of chocolate and cocoa may be harmful during pregnancy

and breast feeding.

Harvesting cocoa, breaking ripe pods Starting a fermentation heap

Box fermentation typesIndustrial sized fermentation

Paullinia sorbilis(Sapindaceae)

Guarana

Native climbing shrub in Brazil and Venezuela.It blooms in June.12 mm long boll in it 1-3 seed development.The fruit is red.Fresh crop is red, brown is dried.2 cotyledons are develop.

Content: caffeine 4-8%tannins 8% (d-catechin)saponin 0,06%fat (3%), resin (7-8%), red colour, starch,mucus, dextrine

Pasta guarana is official in Ph.Hg III.

Guarana is used in sweetened or carbonated soft drinks and energy shots.Generally, South America obtains most of its caffeine from guarana.

As guarana is rich in caffeine, it is of interest for its potential effects on cognition.

Guarana increases the memory retention and physical endurance.

In 2007 a human pilot study assessed acute behavioral effects to four doses(37.5 mg, 75 mg, 150 mg and 300 mg) of guarana extract.

Memory, alertness and mood were increased by the two lower doses, confirmingprevious results of cognitive improvement following 75 mg guarana.

In the United States, guarana has received the designation of „generally recognizedas safe" by the American Food and Drug Administration.

Guarana may affect how quickly the body perceives itself to be full.

Guarana extract reduced aggregation of platelets and decreased plateletthromboxane formation from arachidonic acid by 78 % below control values. It isnot known if such platelet action has any effect on the risk of heart attack orischemic stroke.

Paullinia sorbilis(Sapindaceae)

Guarana

Paullinia sorbilis(Sapindaceae)

Guarana

The seeds gathered from the soaked gvarana crops are roasted, crushed and then mixedwith water are rolled into dough-like paste.

Often starch is added to the guarana powder. It is formed to rod shape. (10-20 cm long,3-4 cm wide, 100-500 g weight). The rod shape is the commercial product.

Cyanogenic glycosides→ HCN (blue acid)

Mustard oil-glycosides:→ (glucosinolates)

*

More than 60 plant families are known to contain cyanogenicglycosides in more than 750 species.

*

!

Route of HCN in plants

HCN is not toxic for the plant, because asparagine acid is formed from HCN.

*

Biosynthesis of linamarin

cyanogenic glycoside

(Flax seed)

*

Cyanogenesis is frequent in the plant kingdom50 seeds are lethal for adults, 10 seeds for children!

Prunus amygdalus Batsch.Rosaceae

Amygdalae semenAlmond seed

Prunus amygdalus var. sativa dulce does not contain cyanogenicglycosidesPrunus amygdalus var. amara contains 3-5 % of amygdalin cyanogenicglycoside, from this quantity 0.2-0.3 % is the hydrocyanic acid.

Prunus amygdalus Batsch.Rosaceae

Amygdalae semenAlmond seed

Products

Oleum amygdalaeAqua amygdalarum amarum -1% HCN after steam destillation.LAETRILE / vitamin B17 – amygdalin product.

Farina amygdalarum – protein rich product seed mass is native substance ofcosmetics .

Biological activity of vitamin B17Laetrile has a dangerous componentcyanide locked away inside. Theonly way that it can get unlockedand come out is when the laetrilecomes into contact with a cancerouscell.Cancer cells have a beta-glucosidase enzyme that unlocksthat cyanide, and the cyanide comesout and destroys the cancer cells.

ExplanationWhen the cyanide comes out thecancer cells, rhodanase andneutralizing substance also comeout from normal cells that preventsthe cyanide from harming anynearby healthy cells. Isothyocyanatewill be formed.Although this is not true!

The detoxicating processes are connected with therodanase enzyme in the mammals.Detoxication needs a sulphur donor.Intravenously sodiumthiosuphate is the clinicalantidots of hydrocyanic acid poisoning.CN- + Na2S2O3 = SCN- + Na2SO3

Prunus spinosa L.Rosaceae

Pruni spinosae flosblackthorn / wild plum

The plant is native in European bushy shrubby slopes. It flowers in April-May, beforeleafing. Fresh flowers have benzaldehyde odor.The white, 1 cm long flowers have free petals and many stamens. Their pistil is incentral position.

Contains: amygdalin cyanogenic glycosideflavonoid: kempferol

kempferin (glycozide)quercetin,quercitrin,rutinhyperozid

Prunus spinosa L.Rosaceae

Pruni spinosae flosblackthorn / wild plum

Confusing synonime: Acaciae flos

Products

It is official in FoNo. IV. as the constituent ofSpecies cynosbati composita. Flowers areapplied in blood-purifying tea mixtures ashypotensive and aperient. Blackthorn brandy

Circa 30 species can be found in the plant kingdom.

Brassicaceae Sinapis species mustard(Cruciferae) Brassica species black radish

cauliflowercabbage white and redkohlrabisavoyhorse radish

Mustard oil and its glycosides

TropaeolaceaeCapparaceaeEuphorbiaceaeResedaceae

Effects:

1. On plant: increases the plant resistance.

1. On human body:

A / Curative effectsappetizer: stomachicum.→ spiceantibacterial activity: disinfectantskin irritant: rheuma creamhyperaemia: neuralgia→ embrocation

B / Toxic effects:antithyreoid→ goitre / strumapustula → necrosis

Mustard oil glycosides

Brassica nigra L.Brassicaceae

Sinapis nigrae semenblack mustard

The plant is native in Europe. Plant is annual, withshort breeding season (110-130 days).

It has stake-like tap root. Leaves are pinafitid,joined. Petals are vivid yellow, having 4 mainstamens.

The flowers are good melliferous plut.

Important spice.

Drug is the semen.

Brassica nigra L.Brassicaceae

Sinapis nigrae semenblack mustard

Contains: 7% sinigrin ( glycoside )0.6-1.2% mustard oil /volatile/ from sinigrin-glycosides./20-40% fatty oils /eruca acid, oil acid, linolenic acid/

sinapin (sinapin acid-choline ester)sinapin acid (4-oxi-3,5-dimetoxi-cinnamonic acid)

myrosinase, mucilagepalmitic acid, arachidonic acid

Galenus’ product: Spiritus sinapis – against rheuma -Charta sinapisataspice – stomachicum

Cultivation: Sinapis nigra x Sinapis rapa ssp. Campester are crossbreaded

Sinapis alba L.Brassicaeae

Sinapis albae semenWhite mustard seed

The plant is native in America and India.

Seeds contain glycoside sinalbin and myrosin aswell as isothiocyanate and sinapine hydrogensulfate. (English mustard)

When the seed is treated with alkaline, the productwill be yellow because of sulfur (sinalbinglycoside).

X+ = sinapin

Sinapis alba L.Brassicaeae

Sinapis albae semenWhite mustard seed

Contains: 2-5 % sinalbin~ 1% mustard oil (volatile)20-30 % fatty oilmyrosinasemucilage, protein

Application: stomachicumchreme from whiteand black mustard seed

Effectiveness: increases secretion of salivaincreases bowel motility andbile secretionhas positive inotropic activity

Tropeolum majus L.Geraniales

This plant is native in America. Tropeolum majus is anornamental plant.

The plant is also a climber. It has a shell form letters andspurred yellowish-reddish flowers.

Contains 0.03 % volatile oils

The main active component is: glucotropeolin (glucosinolate),from this benzyl-mustard oil is formed by myrosinase activity.

Antibacterial effect of benzyl-mustard oil isestablished.

Harmful to both Gram (+), and Gram (-)bacteria.

THE ROLE OF ANTIOXIDANTS IN SIGNAL TRANSDUCTION

Most glucosinolates are converted enzymatically to their cognate isothiocyanates(ITC) by the coexisting but normally segregated plant enzyme myrosinase (whichis released when food is prepared or chewed), and by the flora of the humangastrointestinal tract.

Isothiocyanate is the chemical group –N=C=S, formed by substituting sulfur withoxygen in the isocyanate group.

Many natural isothiocyanates from plants are produced by enzymatic conversion ofmetabolites called glucosinolates.

These natural isothiocyanates, such as allyl isothiocyanate, are also known asmustard oils.

isothiocyanate

Small molecules, such as fenethyl-isothiocyanate,sulforaphane and indol-3-carbinol can be absorbed fromfood.

Following rapid intracellular accumulations,isothiocyanates are formed and conjugated to glutathioneby glutathione-S-transferase.

After these conjugation reactions, the conjugates arefurther metabolized. In these processes mercapturic acidis formed by the actions of γ-glutamyltranspeptidase,cysteinylglycinase and N-acetyltransferase.

Raphanus sativus L. var. nigerIn folk medicine black radish (Raphanus sativus L. varniger) root has been used for thousands of years.

A widely planted root all over the world belongs to theCruciferae family.

Black radish was very popular vegetable and folk medicineamong Hungarians and other European populations.

The natural drug has been used against abdominalinflation, insufficient digestion and for the inhibition ofgallstone formation and for the stimulation of bilesecretion.

Raphanus sativus L. var. niger

This drug contains mainly glucosinolates and/or derivatives(isothiocyanates, nitriles, cyano-epithioalkanes formed during

enzymatic hydrolysis by myrosinase)

essential oils, polyphenols and flavonoids phenolic acids

enzymes, enzyme-inhibitors,

microelements, vitamins: B-C,

phytoncid, raphanin.

The most important flavonoid component of black radish iskaempferol (21.1 mg/kg) originating from the fresh edible part of the

plant.

BIOACTIVE COMPOUNDS OF BLACK REDISH ROOT

Glucosinolates (mg) n.d. n.d.

Ascorbic acid (mg) 5.0 0.08 81.6

Carotene (mg) 0.02 0.002 0.33

Tocopherols (mg) 0.31 0.03 5.06

Total polyphenols (mg) 25.5 5.2 415.9

Quercetin (mg) 0.066 0.022 1.08

Kempferol (mg) 0.495 0.252 8.08

mg/100 gmg/100 mlComponents

by Andrea Lugasi

Antioxidant effect of bile granule with Raphanus sativusniger in vitro

Bioactive, non nutrient compounds ofblack radish are active hydrogen donorsand they have a reducing power property,so they act as primary and secondaryantioxidants in lipid peroxidation.

In a chemiluminescent study thesample showed free radical scavengingactivity.Scavenging juice activity in H2O2/.OH–luminol system was measured.

New balance will be formed after three month long treatment.

Usual laboratory parameters wereanalyzed in the sera.Most serum parameters such as ions,hemoglobin, hematocrit, liverfunction enzymes did not changeduring the treatment.After 6 months some serumparameters such as glucose,hemoglobin-Alc, glycohemoglobin,cholesterol and triglyceride levelsimproved, and the majority of thepatients reported the elimination ofthe abdominal inconveniences inboth diabetic groups.

Patients were under regular medical controland received adequate treatment ofdiabetes.Blood samples were collected before the firstadministration of Raphacol, and after 3 and6 months.

Beneficial effects on diabetes mellitus

NOT BENEFICIAL EFFECTS OF ISOTHIOCYANATES IN IBDPATIENTS

Patients were under regular medical control andreceived adequate treatment of IBD.Blood samples were collected before the firstadministration of Raphacol, and after 3, 6, 9and 12 months.

Usual laboratory parameters wereanalyzed in the sera. Most serumparameters such as ions, hemoglobin,hematocrit, liver function enzymes didnot change during the treatment.After 6 months, some serumparameters such as glucose, Hgb-Alc,glycohemoglobin, cholesterol, andtriglyceride levels improved and themajority of the patients reported theelimination of the abdominalinconveniences in IBD.

Bile acid concentration of plasma was higher than the normalvalue after 12 months long treatent.

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